tbuckley/cabot-search huggingface dataset:
Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance)
Authors: Qiao-Li Wang, Chao Ma, Chen Yuan, Qian Shi, Brian M. Wolpin, Yin Zhang, Charles S. Fuchs, Jeffrey Meyer, Tyler Zemla, En Cheng, Priya Kumthekar, Katherine A. Guthrie, Felix Couture, Philip Kuebler, Pankaj Kumar, Benjamin Tan, Smitha Krishnamurthi, Richard M. Goldberg, Alan Venook, Charles Blanke, Anthony F. Shields, Eileen M. O'Reilly, Jeffrey A. Meyerhardt, Kimmie Ng
Journal: Clinical Cancer Research (2023)

Abstract Purpose: To assess whether higher plasma 25-hydroxyvitamin D [25(OH)D] is associated with improved outcomes in colon cancer and whether circulating inflammatory cytokines mediate such association. Experimental Design: Plasma samples were collected from 1,437 patients with stage III colon cancer enrolled in a phase III randomized clinical trial (CALGB/SWOG 80702) from 2010 to 2015, who were followed until 2020. Cox regressions were used to examine associations between plasma 25(OH)D and disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR). Mediation analysis was performed for circulating inflammatory biomarkers of C-reactive protein (CRP), IL6, and soluble TNF receptor 2 (sTNF-R2). Results: Vitamin D deficiency [25(OH)D &amp;lt;12 ng/mL] was present in 13% of total patients at baseline and in 32% of Black patients. Compared with deficiency, nondeficient vitamin D status (≥12 ng/mL) was significantly associated with improved DFS, OS, and TTR (all Plog-rank&amp;lt;0.05), with multivariable-adjusted HRs of 0.68 (95% confidence interval, 0.51–0.92) for DFS, 0.57 (0.40–0.80) for OS, and 0.71 (0.52–0.98) for TTR. A U-shaped dose–response pattern was observed for DFS and OS (both Pnonlinearity&amp;lt;0.05). The proportion of the association with survival that was mediated by sTNF-R2 was 10.6% (Pmediation = 0.04) for DFS and 11.8% (Pmediation = 0.05) for OS, whereas CRP and IL6 were not shown to be mediators. Plasma 25(OH)D was not associated with the occurrence of ≥ grade 2 adverse events. Conclusions: Nondeficient vitamin D is associated with improved outcomes in patients with stage III colon cancer, largely independent of circulation inflammations. A randomized trial is warranted to elucidate whether adjuvant vitamin D supplementation improves patient outcomes.
T helper 2 cells in asthma
Authors: James A. Harker, Clare M. Lloyd
Journal: The Journal of Experimental Medicine (2023)

Allergic asthma is among the most common immune-mediated diseases across the world, and type 2 immune responses are thought to be central to pathogenesis. The importance of T helper 2 (Th2) cells as central regulators of type 2 responses in asthma has, however, become less clear with the discovery of other potent innate sources of type 2 cytokines and innate mediators of inflammation such as the alarmins. This review provides an update of our current understanding of Th2 cells in human asthma, highlighting their many guises and functions in asthma, both pathogenic and regulatory, and how these are influenced by the tissue location and disease stage and severity. It also explores how biologics targeting type 2 immune pathways are impacting asthma, and how these have the potential to reveal hitherto underappreciated roles for Th2 cell in lung inflammation.
Characterization of a Musculoskeletal Syndrome of Enthesitis and Arthritis in Patients With Atopic Dermatitis Treated With Dupilumab, an Interleukin‐4/13 Inhibitor
Authors: Catherine D. Hughes, Joseph Nathan, Libin Mathew, Andrew E. Pink, Richard T. Woolf, Catherine Smith, Bina Menon, Bruce Kirkham
Journal: Arthritis & Rheumatology (2023)

To characterize the presentation and outcomes of patients with atopic dermatitis (AD) who developed musculoskeletal symptoms after treatment with dupilumab, a human IgG4 monoclonal antibody that blocks the functions of interleukin-4 (IL-4) and IL-13, key pathologic pathways in AD.This article reports an observational cohort of patients receiving dupilumab who developed new-onset musculoskeletal symptoms after dupilumab therapy at our center. All patients had a comprehensive rheumatologic history and examination, with imaging by ultrasonography (US) or magnetic resonance imaging (MRI) in most patients.Between October 2018 and February 2021, we recorded 470 patients with AD commencing dupilumab treatment from routine clinical care records. Of 36 patients referred for rheumatologic assessment, we identified 26 patients (14 male, 12 female) with a musculoskeletal syndrome of inflammatory enthesitis, arthritis, and/or tenosynovitis. Clinical findings were confirmed by US and MRI. All patients had very good response to dupilumab treatment, and no specific predictors of musculoskeletal syndrome were noted. Symptoms were mild in 16 patients, moderate in 6 patients, and severe in 4 patients. Receipt of nonsteroidal antiinflammatory drugs or cyclooxygenase 2 inhibitors, reduction of dupilumab dose/frequency, and cessation of dupilumab therapy led to improvement, but moderate or severe symptoms persisted for many months.We report a new musculoskeletal syndrome of inflammatory enthesitis/arthritis/tenosynovitis in some patients receiving the IL-4 receptor antagonist dupilumab. This response to a cytokine-targeting therapy provides key insights into the pathogenesis of enthesitis.
Differential impact of dual-active ingredient long-lasting insecticidal nets on primary malaria vectors: a secondary analysis of a 3-year, single-blind, cluster-randomised controlled trial in rural Tanzania
Authors: Nancy S Matowo, Manisha A Kulkarni, Louisa A Messenger, Mohamed Jumanne, Jackline Martin, Elizabeth Mallya, Eliud Lukole, Jacklin F Mosha, Oliva Moshi, Boniface Shirima, Robert Kaaya, Mark Rowland, Alphaxard Manjurano, Franklin W Mosha, Natacha Protopopoff
Journal: The Lancet Planetary Health (2023)
Serosurveillance of SARS-CoV-2 in Welsh Blood Donors: Establishment of the surveillance system and results up to November 2022
Authors: Sophie Harker, Siân Elizabeth James, James Murphy, Ben Davies, Catherine Moore, Brian P Tennant, John Geen, Daniel Thomas
Journal: Eurosurveillance (2023)

Background In 2020, Wales experienced some of the highest rates of confirmed COVID-19 cases in Europe. We set up a serosurveillance scheme using residual samples from blood donations to inform the pandemic response in Wales. Aim To identify changes in SARS-CoV-2 antibody seroprevalence in Wales by time, demography and location. Methods Residual samples from blood donations made in Wales between 29 June 2020 and 20 November 2022 were tested for antibodies to the nucleocapsid antigen (anti-N) of SARS-CoV-2, resulting from natural infection. Donations made between 12 April 2021 and 20 November 2022 were also tested for antibodies to the spike antigen (anti-S) occurring as a result of natural infection and vaccination. Results Age-standardised seroprevalence of anti-N antibodies in donors remained stable (4.4–5.5%) until November 2020 before increasing to 16.7% by February 2021. Trends remained steady until November 2021 before increasing, peaking in November 2022 (80.2%). For anti-S, seroprevalence increased from 67.1% to 98.6% between May and September 2021, then remained above 99%. Anti-N seroprevalence was highest in younger donors and in donors living in urban South Wales. In contrast, seroprevalence of anti-S was highest in older donors and was similar across regions. No significant difference was observed by sex. Seroprevalence of anti-N antibodies was higher in Black, Asian and other minority ethnicities (self-reported) compared with White donors, with the converse observed for anti-S antibodies. Conclusion We successfully set up long-term serological surveillance of SARS-CoV-2 using residual samples from blood donations, demonstrating variation based on age, ethnicity and location.
Novel protective retrieval bag for safe removal of gastric gastrointestinal stromal tumor after endoscopic full-thickness resection
Authors: Miguel Fraile-López, Noriya Uedo, Yoji Takeuchi, Tomoki Michida
Journal: Endoscopy (2023)

Endoscopic resection of gastric subepithelial lesions (GSELs) is gaining in popularity owing to its good results and less invasive nature compared to surgery [1] [2]. However, extracting specimens through the gastroesophageal junction or upper esophageal sphincter can be technically challenging and may cause fragmentation or capsule damage, which may lead to an inaccurate histopathological evaluation [2].
An unusual case of isolated serum γ-glutamyl transferase elevation: slight abnormality also should not be taken lightly
Authors: Ke Chen, Yi Lu, Jianyu Yang, Yongwei Sun, Xiujiang Yang
Journal: Endoscopy (2023)

A 75-year-old man was admitted to our hospital for isolated serum γ-glutamyl transpeptidase (GGT, 147 U/L) elevation, with fluctuation in the past 2 years ([Fig. 1]). His alanine aminotransferase, glutamic transaminase, bilirubin level, and tumor markers were all in normal range. He had no symptoms, except for mild soreness in the right waist for 2 months. Magnetic resonance imaging (MRI) revealed a low signal in T2 W with dilation of the common bile duct (CBD) to 12 mm and enlargement of the gallbladder ([Fig. 2]). Hence, endoscopic ultrasound (EUS) was performed for a definite diagnosis. The major papilla was small with a normal surface ([Fig. 3]). In the distal CBD, a hypoechoic nodule (13.1 × 7.2 mm) was found wriggling along with the sphincter contraction ([Fig. 4 a]). Contrast-enhanced EUS showed the enhancement of the lesion, but the degree was weaker than the peripheral pancreas ([Fig. 4 b], [Video 1]).
Projecting future risk of dengue related to hydrometeorological conditions in mainland China under climate change scenarios: a modelling study
Authors: Chuanxi Li, Zhao Liu, Wen Li, Yuxi Lin, Liangyu Hou, Shuyue Niu, Yue Xing, Jianbin Huang, Yidan Chen, Shangchen Zhang, Xuejie Gao, Ying Xu, Can Wang, Qi Zhao, Qiyong Liu, Wei Ma, Wenjia Cai, Peng Gong, Yong Luo
Journal: The Lancet Planetary Health (2023)

BackgroundWe have limited knowledge on the impact of hydrometeorological conditions on dengue incidence in China and its associated disease burden in a future with a changed climate. This study projects the excess risk of dengue caused by climate change-induced hydrometeorological conditions across mainland China.MethodsIn this modelling study, the historical association between the Palmer drought severity index (PDSI) and dengue was estimated with a spatiotemporal Bayesian hierarchical model from 70 cities. The association combined with the dengue-transmission biological model was used to project the annual excess risk of dengue related to PDSI by 2100 across mainland China, under three representative concentration pathways ([RCP] 2·6, RCP 4·5, and RCP 8·5).Findings93 101 dengue cases were reported between 2013 and 2019 in mainland China. Dry and wet conditions within 3 months lag were associated with increased risk of dengue. Locations with potential dengue risk in China will expand in the future. The hydrometeorological changes are projected to substantially affect the risk of dengue in regions with mid-to-low latitudes, especially the coastal areas under high emission scenarios. By 2100, the annual average increased excess risk is expected to range from 12·56% (95% empirical CI 9·54–22·24) in northwest China to 173·62% (153·15–254·82) in south China under the highest emission scenario.InterpretationHydrometeorological conditions are predicted to increase the risk of dengue in the future in the south, east, and central areas of mainland China in disproportionate patterns. Our findings have implications for the preparation of public health interventions to minimise the health hazards of non-optimal hydrometeorological conditions in a context of climate change.FundingNational Natural Science Foundation of China.
Evidence on Effectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma—Reply
Authors: Joseph J. Zhao, Filippo Pietrantonio, Raghav Sundar
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Efficacy of Empagliflozin in Patients With Heart Failure Across Kidney Risk Categories
Authors: Javed Butler, Milton Packer, Tariq Jamal Siddiqi, Michael Böhm, Martina Brueckmann, James L. Januzzi, Subodh Verma, Ingrid Gergei, Tomoko Iwata, Christoph Wanner, João Pedro Ferreira, Stuart J. Pocock, Gerasimos Filippatos, Stefan D. Anker, Faiez Zannad
Journal: Journal of the American College of Cardiology (2023)

Empagliflozin reduces the risk of major heart failure outcomes in heart failure with reduced or preserved ejection fraction. The goal of this study was to evaluate the effect of empagliflozin across the spectrum of chronic kidney disease in a pooled analysis of EMPEROR-Reduced and EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced or Preserved Ejection Fraction, respectively). A total of 9,718 patients were grouped into Kidney Disease Improving Global Outcomes (KDIGO) categories based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio into low-, moderate-, high-, and very–high-risk categories, comprising 32.0%, 29.1%, 21.9%, and 17.0% of the participants, respectively. In the placebo arm, when compared with lower risk categories, patients at higher risk experienced a slower rate of decline in eGFR, but a higher risk of a composite kidney event. Empagliflozin reduced the risk of cardiovascular death or heart failure hospitalizations similarly in all KDIGO categories (HR: 0.81; 95% CI: 0.66-1.01 for low-; HR: 0.63; 95% CI: 0.52-0.76 for moderate-; HR: 0.82; 95% CI: 0.68-0.98 for high-; and HR: 0.84; 95% CI: 0.71-1.01 for very–high-risk groups; P trend = 0.30). Empagliflozin reduced the rate of decline in eGFR whether it was estimated by chronic slope, total slope, or unconfounded slope. When compared with the unconfounded slope, the magnitude of the effect on chronic slope was larger, and the effect on total slope was smaller. In EMPEROR-Reduced, patients at lowest risk experienced the largest effect of empagliflozin on eGFR slope; this pattern was not observed in EMPEROR-Preserved. The benefit of empagliflozin on major heart failure events was not influenced by KDIGO categories. The magnitude of the renal effects of the drug depended on the approach used to calculate eGFR slopes.
Correcting gradient-based interpretations of deep neural networks for genomics
Authors: Antonio Majdandzic, Chandana Rajesh, Peter K. Koo
Journal: Genome biology (2023)

Post hoc attribution methods can provide insights into the learned patterns from deep neural networks (DNNs) trained on high-throughput functional genomics data. However, in practice, their resultant attribution maps can be challenging to interpret due to spurious importance scores for seemingly arbitrary nucleotides. Here, we identify a previously overlooked attribution noise source that arises from how DNNs handle one-hot encoded DNA. We demonstrate this noise is pervasive across various genomic DNNs and introduce a statistical correction that effectively reduces it, leading to more reliable attribution maps. Our approach represents a promising step towards gaining meaningful insights from DNNs in regulatory genomics.
Barriers to Disclosure of Disability and Request for Accommodations Among First-Year Resident Physicians in the US
Authors: Karina Pereira-Lima, Lisa M. Meeks, Katherine E. T. Ross, Jasmine R. Marcelin, Lydia Smeltz, Elena Frank, Srijan Sen
Journal: JAMA Network Open (2023)

Importance Ensuring access to accommodations is critical for resident physicians and their patients. Studies show that a large proportion of medical trainees with disabilities do not request needed accommodations; however, drivers of nonrequests are unknown. Objective To assess the frequency of accommodation requests among first-year resident physicians (ie, interns) with disabilities and to identify possible drivers of nonrequest for needed accommodations. Design, Setting, and Participants As part of the Intern Health Study, a longitudinal cohort study of first-year resident physicians, residents at 86 surgical and nonsurgical residency programs in 64 US institutions provided demographic and training characteristics 2 months prior to matriculation (April-May 2021). At the end of their intern year (June 2022), participants completed a new survey with questions about disability-related information, including disability status, disability type, whether they received accommodations, and if not, reasons for nonaccommodation. Poststratification and attrition weights were used to estimate the frequency of accommodation requests and reasons for not requesting accommodations. Interns reporting at least 1 disability were included in the analysis. Main Outcomes and Measures Prevalence of reported disabilities, residency specialties distribution, frequency of accommodation requests, and reasons for nonaccommodation among resident physicians with disabilities. Results Among the 1486 resident physicians who completed the baseline survey, 799 (53.8%) replied to the disability questions. Of those, 94 interns (11.8%; weighted number, 173 [11.9%]) reported at least 1 disability and were included in the present study (weighted numbers, 91 [52.6%] men, 82 [47.4%] women, mean [SD] age, 28.6 [3.0] years). Among interns with reported disability and need for accommodations (83 of 173 [48.0%]), more than half (42 [50.6%]) did not request them. The most frequently reported reasons for not requesting needed accommodations were fear of stigma or bias (25 [59.5%]), lack of a clear institutional process for requesting accommodations (10 [23.8%]), and lack of documentation (5 [11.9%]). Conclusions and Relevance Program directors should investigate cultural and structural factors within their programs that contribute to an environment where residents do not feel safe or supported in disclosing disability and requesting accommodation and review their disability policies for clarity.
Underwater precutting endoscopic mucosal resection using a multifunctional snare for a large colonic laterally spreading tumor
Authors: Kazuo Shiotsuki, Yorinobu Sumida, Mitsuru Esaki, Yosuke Minoda, Shin-ichiro Fukuda, Eikichi Ihara, Hirotada Akiho
Journal: Endoscopy (2023)

Underwater endoscopic mucosal resection (UEMR) is a recently developed procedure characterized by resection of the colon polyps immersed in water. Thanks to the "floating effect" on the mucosa and submucosa, UEMR allows snaring the lesion much more easily compared to conventional EMR [1] [2]. However, it is technically challenging to use UEMR for large colon polyps, especially a large colonic laterally spreading tumor (LST), due to the risk of incomplete resection. In contrast, precutting EMR (PEMR) with a planned partial circumferential mucosal incision is reportedly useful for en bloc resection of a colonic LST [3]. We considered that UEMR would complement PEMR, exerting synergistic effects. Here we present a case of a large colonic LST successfully treated by UEMR in conjunction with underwater PEMR ([Video 1]).
Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention
Authors: Nora D. Volkow, Carlos Blanco
Journal: World Psychiatry (2023)

Substance use disorders (SUDs) are highly prevalent and exact a large toll on individuals’ health, well‐being, and social functioning. Long‐lasting changes in brain networks involved in reward, executive function, stress reactivity, mood, and self‐awareness underlie the intense drive to consume substances and the inability to control this urge in a person who suffers from addiction (moderate or severe SUD). Biological (including genetics and developmental life stages) and social (including adverse childhood experiences) determinants of health are recognized factors that contribute to vulnerability for or resilience against developing a SUD. Consequently, prevention strategies that target social risk factors can improve outcomes and, when deployed in childhood and adolescence, can decrease the risk for these disorders. SUDs are treatable, and evidence of clinically significant benefit exists for medications (in opioid, nicotine and alcohol use disorders), behavioral therapies (in all SUDs), and neuromodulation (in nicotine use disorder). Treatment of SUDs should be considered within the context of a Chronic Care Model, with the intensity of intervention adjusted to the severity of the disorder and with the concomitant treatment of comorbid psychiatric and physical conditions. Involvement of health care providers in detection and management of SUDs, including referral of severe cases to specialized care, offers sustainable models of care that can be further expanded with the use of telehealth. Despite advances in our understanding and management of SUDs, individuals with these conditions continue to be stigmatized and, in some countries, incarcerated, highlighting the need to dismantle policies that perpetuate their criminalization and instead develop policies to ensure support and access to prevention and treatment.